Abstract 1524: Expression of GDNF and its receptors in glioblastoma

Abstract

Abstract Introduction: Glioblastoma is the most aggressive primary brain cancer and one of the most lethal types of cancer overall. Despite multimodal treatment strategies, the prognosis is poor with a median survival of approx. 15 months. Although neurotrophic factors are of major importance in the nervous system, their role in brain cancer is still not fully understood. We focused on the glial cell line-derived neurotrophic factor (GDNF), which has been shown to play a role in growth and migration in glioblastoma. The aim of this study was to investigate the expression of GDNF and it primary receptor GFRA1, as well as the other GDNF family receptors GFRA2-4 and RET. Methods: Tissue sections from 10 glioblastoma patients were stained with antibodies against GDNF and each of the receptors. GDNF stainings were performed on frozen tissue slides, while receptor stainings were performed on formalin-fixed paraffin-embedded tissue sections. The area fractions of positive staining were quantified with a software-based classifier. Double immunofluorescence stainings with the different markers and Iba1 as well as GFAP were performed to assess expression in microglia/macrophages and tumor cells, respectively. Results: GDNF staining was observed in five of ten patient specimens, whereas GFRA1 and GFRA2 staining was observed in all samples. GFRA1 and GFRA2 staining was seen in the membrane and cytoplasm with a mean area fraction of GFRA1 staining at 31% (range: 7-56%), and a mean area fraction of GFRA2 staining at 3% (range: 0.2-7%). GFRA3, GFRA4 and RET were not expressed in glioblastoma tissue. Double immunofluorescence stainings demonstrated co-expression of GFRA1 and GFAP, while co-expression of GFRA1 and IBA1 was limited. Conclusion and perspectives: Our results suggest that GDNF and GFRA1 are widely expressed in glioblastoma tumor tissue, but GFRA2 is also expressed and may play a role in glioblastoma biology. Additional stainings are being established to clarify cellular expression and expression levels of GDNF and its receptors. Citation Format: Jesper D. Ewald, Arnon M. Knudsen, Bjarne W. Kristensen. Expression of GDNF and its receptors in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1524.